• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Hormad1 mutation disrupts synaptonemal complex formation, recombination, and chromosome segregation in mammalian meiosis.

Meiosis is unique to germ cells and essential for reproduction. During the first meiotic division, homologous chromosomes pair, recombine, and form chiasmata. The homologues connect via axial elements and numerous transverse filaments to form the synaptonemal complex. The synaptonemal complex is a critical component for chromosome pairing, segregation, and recombination. We previously identified a novel germ cell-specific HORMA domain encoding gene, Hormad1, a member of the synaptonemal complex and a mammalian counterpart to the yeast meiotic HORMA domain protein Hop1. Hormad1 is essential for mammalian gametogenesis as knockout male and female mice are infertile. Hormad1 deficient (Hormad1(-/) (-)) testes exhibit meiotic arrest in the early pachytene stage, and synaptonemal complexes cannot be visualized by electron microscopy. Hormad1 deficiency does not affect localization of other synaptonemal complex proteins, SYCP2 and SYCP3, but disrupts homologous chromosome pairing. Double stranded break formation and early recombination events are disrupted in Hormad1(-/) (-) testes and ovaries as shown by the drastic decrease in the γH2AX, DMC1, RAD51, and RPA foci. HORMAD1 co-localizes with γH2AX to the sex body during pachytene. BRCA1, ATR, and γH2AX co-localize to the sex body and participate in meiotic sex chromosome inactivation and transcriptional silencing. Hormad1 deficiency abolishes γH2AX, ATR, and BRCA1 localization to the sex chromosomes and causes transcriptional de-repression on the X chromosome. Unlike testes, Hormad1(-/) (-) ovaries have seemingly normal ovarian folliculogenesis after puberty. However, embryos generated from Hormad1(-/) (-) oocytes are hyper- and hypodiploid at the 2 cell and 8 cell stage, and they arrest at the blastocyst stage. HORMAD1 is therefore a critical component of the synaptonemal complex that affects synapsis, recombination, and meiotic sex chromosome inactivation and transcriptional silencing.

Pubmed ID: 21079677

Authors

  • Shin YH
  • Choi Y
  • Erdin SU
  • Yatsenko SA
  • Kloc M
  • Yang F
  • Wang PJ
  • Meistrich ML
  • Rajkovic A

Journal

PLoS genetics

Publication Data

November 16, 2010

Associated Grants

  • Agency: NICHD NIH HHS, Id: HD054829

Mesh Terms

  • Aneuploidy
  • Animals
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins
  • Chromosome Segregation
  • DNA-Binding Proteins
  • Embryonic Development
  • Female
  • Fetus
  • Male
  • Meiosis
  • Mice
  • Mutation
  • Nuclear Proteins
  • Oocytes
  • Organ Specificity
  • Ovary
  • Phosphorylation
  • Protein Transport
  • Protein-Serine-Threonine Kinases
  • RNA, Messenger
  • Recombination, Genetic
  • Sex Chromosomes
  • Spermatogenesis
  • Spermatozoa
  • Synaptonemal Complex
  • Tumor Suppressor Proteins